Chlamydia vaccine based on targeting momp vs4 antigen to antigen presenting cells

Abstract

Chlamydiae are intracellular bacterial pathogens responsible for a variety of infections. The inventors produced an antibody that is directed against a surface antigen (i.e., CD40) of an antigen presenting cell (i.e., dendritic cell) wherein the heavy chain and/or light chain is conjugated to the MOMP VS4 domain of Chlamydia trachomatis for its use as vaccine.

1 .- 25 . (canceled). 
     
     
         26 . An antibody that is directed against a surface antigen of an antigen presenting cell wherein the heavy chain and/or the light chain is conjugated or fused to a VS4 polypeptide having at least 80% of identity with the amino acid sequence that ranges from the amino acid residue at position 282 to the amino acid residue at position 358 in SEQ ID NO:1. 
     
     
         27 . The antibody of  claim 26  that is an IgG antibody. 
     
     
         28 . The antibody of  claim 26  that is a chimeric antibody, in particular a chimeric mouse/human antibody or a humanized antibody. 
     
     
         29 . The antibody of  claim 26  that is selected from an antibody that specifically binds to DC immunoreceptor (DCIR), MHC class I, MHC class II, CD1, CD2, CD3, CD4, CD8, CD11b, CD14, CD15, CD16, CD19, CD20, CD29, CD31, CD40, CD43, CD44, CD45, CD54, CD56, CD57, CD58, CD83, CD86, CMRF-44, CMRF-56, DCIR, DC-ASPGR, CLEC-6, CD40, BDCA-2, MARCO, DEC-205, mannose receptor, Langerin, DECTIN-1, B7-1, B7-2, IFN-y receptor and IL-2 receptor, ICAM-1, Fey receptor, LOX-1, and ASPGR. 
     
     
         30 . The antibody of  claim 26  that is specific for CD40. 
     
     
         31 . The antibody of  claim 26  that is specific for CD40 and that derives:
 from the 12E12 antibody and comprises:
 a heavy chain comprising the complementarity determining regions CDR1H, CDR2H and CDR3H, the CDR1H having the amino acid sequence GFTFSDYYMY (SEQ ID NO:3), the CDR2H having the amino acid sequence YINSGGGSTYYPDTVKG (SEQ ID NO:4), and the CDR3H having the amino acid sequence RGLPFHAMDY (SEQ ID NO:5), 
 and a light chain comprising the complementarity determining regions CDR1L, CDR2L and CDR3L, the CDR1L having the amino acid sequence SASQGISNYLN (SEQ ID NO:6) the CDR2L having the amino acid sequence YTSILHS (SEQ ID NO:7) and the CDR3L having the amino acid sequence QQFNKLPPT (SEQ ID NO:8); 
 
 or from the 1166 antibody and comprises:
 a heavy chain comprising the complementarity determining regions CDR1H, CDR2H and CDR3H, the CDR1H having the amino acid sequence GYSFTGYYMH (SEQ ID NO:9), the CDR2H having the amino acid sequence RINPYNGATSYNQNFKD (SEQ ID NO:10), and the CDR3H having the amino acid sequence EDYVY (SEQ ID NO:11), and 
 a light chain comprising the complementarity determining regions CDR1L, CDR2L and CDR3L, the CDR1L having the amino acid sequence RSSQSLVHSNGNTYLH (SEQ ID NO:12) the CDR2L having the amino acid sequence KVSNRFS (SEQ ID NO:13) and the CDR3L having the amino acid sequence SQSTHVPWT (SEQ ID NO:14); 
 
 or from the 12B4 antibody and comprises:
 a heavy chain comprising the complementarity determining regions CDR1H, CDR2H and CDR3H, the CDR1H having the amino acid sequence GYTFTDYVLH (SEQ ID NO:15), the CDR2H having the amino acid sequence YINPYNDGTKYNEKFKG (SEQ ID NO:16), and the CDR3H having the amino acid sequence GYPAYSGYAMDY (SEQ ID NO:17), and 
 a light chain comprising the complementarity determining regions CDR1L, CDR2L and CDR3L, the CDR1L having the amino acid sequence RASQDISNYLN (SEQ ID NO:18) the CDR2L having the amino acid sequence YTSRLHS (SEQ ID NO:19) and the CDR3L having the amino acid sequence HHGNTLPWT (SEQ ID NO:20). 
 
 
     
     
         32 . The antibody of  claim 30  wherein the anti-CD40 antibody is selected from the group consisting of selected mAb1, mAb2, mAb3, mAb4, mAb5, and mAb6 as described in Table A. 
     
     
         33 . The antibody of  claim 26  that is a CD40 agonist antibody. 
     
     
         34 . The antibody of  claim 26  that is a CD40 agonist antibody wherein the heavy chain or the light chain of the CD40 agonist antibody (i.e., the chain that is not conjugated or fused to the VS4 polypeptides) is conjugated or fused to a CD40 binding domain of CD40L (SEQ ID NO:2). 
     
     
         35 . The antibody of  claim 26  that is a CD40 agonist antibody whose heavy chain or light chain (i.e., the chain that is not conjugated or fused to the VS4 polypeptides) are conjugated or fused to a CD40 binding domain of CD40L (SEQ ID NO:2), wherein:
 the CD40 binding domain of CD40L is fused to the C-terminus of a light or heavy chain of said CD40 agonist antibody, optionally via a linker; or 
 the heavy chain of the antibody is fused or conjugated to the VS4 polypeptide and the light chain is conjugated or fused to the CD40 binding domain of CD40L (SEQ ID NO:2). 
 
     
     
         36 . The antibody of  claim 26  that is specific for Langerin. 
     
     
         37 . The antibody of  claim 36  that comprises
 a heavy chain comprising the complementarity determining regions CDR1H, CDR2H, and CDR3H of the 15B10 antibody and a light chain comprising the complementarity determining regions CDR1L, CDR2L, and CDR3L of the 15B10 antibody, or 
 a heavy chain comprising the complementarity determining regions CDR1H, CDR2H, and CDR3H of the 2G3 antibody and a light chain comprising the complementarity determining regions CDR1L, CDR2L, and CDR3L of the 2G3 antibody, or 
 a heavy chain comprising the complementarity determining regions CDR1H, CDR2H, and CDR3H of the 4C7 antibody and a light chain comprising the complementarity determining regions CDR1L, CDR2L, and CDR3L of the 4C7 antibody. 
 
     
     
         38 . The antibody of  claim 36  that is selected from the group consisting of selected mAb7, mAb8, mAb9, mAb10, mAb11, and mAb12 as described in Table B. 
     
     
         39 . The antibody of  claim 26  wherein the heavy chain and/or the light chain is fused to the VS4 polypeptide via the linker selected from the group consisting of FlexV1, f1, f2, f3, and f4. 
     
     
         40 . The antibody of  claim 26  that comprises a heavy chain or light chain that is conjugated via a dockerin domain to the cohesion fusion protein that consists of the amino acid sequence as set forth in SEQ ID NO:38. 
     
     
         41 . A nucleic acid that encodes for a heavy chain and/or the light chain of the antibody of  claim 26 . 
     
     
         42 . A vector comprising the nucleic acid of  claim 41 . 
     
     
         43 . A host cell which has been transfected, infected, or transformed by the nucleic acid of  claim 41 . 
     
     
         44 . A host cell which has been transfected, infected, or transformed by the vector of  claim 42 . 
     
     
         45 . A vaccine composition comprising the antibody of  claim 26 . 
     
     
         46 . A method for vaccinating a subject in need thereof against  Chlamydia trachomatis  comprising administering a therapeutically effective amount of the antibody of  claim 26 .